Biomarkers of Calcific Aortic Valve Disease

Abstract

Calcific aortic valve disease (CAVD) is a highly prevalent cardiovascular disorder accounting for a rising economic and social burden on aging populations. In spite of continuing study on the pathophysiology of disease, there remain no medical therapies to prevent the progression of CAVD. The discovery of biomarkers represents a potentially complementary approach in stratifying risk and timing of intervention in CAVD and has the advantage of providing insight into causal factors for the disease. Biomarkers have been studied extensively in atherosclerotic cardiovascular disease, with success as additive for clinical and scientific purposes. Similar research in CAVD is less robust; however, the available studies of biomarkers in CAVD show promise for enhanced clinical decision making and identification of causal factors for the disease. This comprehensive review summarizes available established and novel biomarkers in CAVD, their contributions toward an understanding of pathophysiology, their potential clinical utility, and provides an outline to direct future research in the field.

Keywords: aortic valve; aortic valve stenosis; biomarkers; heart defects, congenital; heart valve diseases.

Conflict of interest statement

Conflicts of Interest Disclosures: None

© 2017 American Heart Association, Inc.

Figures

Figure 1

a simplified schematic for the pathophysiology of CAVD. Mechanical stress results in endothelial damage, allowing penetration and entrapment of lipids into the valve endothelium. Oxidative modification of lipoproteins, and the eventual generation of inflammatory molecules promote invasion of the valve fibrosa by circulating macrophages and T-cells, and result in the activation of resident valve interstitial cells to activated and osteochondrogenic subtypes. Valve interstitial cells may also be activated in response to autocrine signals originating in response to biomechanical stress and valve injury. In coordination with activated valve interstitial cells, invading inflammatory cells and oxidized lipids promote fibrosis of the valve interstitium. Calcificiation is proposed to begin early in the disease process, but is clearly manifest in pathologic specimens for late stage disease as both calcified nodules and skeletal bone.